Fungal plant diseases are controlled by a complex molecular dialogue that involves pathogen effectors able to manipulate plant susceptibility factors at the earliest stages of the interaction. By probing the wheat-Fusarium graminearum pathosystem, we profiled the co-regulations of the fungal and plant proteins shaping the molecular responses of a 96-hour-long infection's dynamics. While no symptoms were yet detectable, fungal biomass swiftly increased along with an extremely diverse set of secreted proteins and candidate effectors supposed to target key plant organelles. Some showed to be early accumulated during the interaction or already present in spores, otherwise stored in germinating spores and detectable in an in vitro F. graminearum exudate. Wheat responses were swiftly set up and were evidenced before any visible symptom. Significant wheat protein abundance changes co-occurred along with the accumulation of putative secreted fungal proteins and predicted effectors. Regulated wheat proteins were closely connected to basal cellular processes occurring during spikelet ontogeny and particular co- regulation patterns were evidenced between chloroplast proteins and fungal proteins harboring a predicted chloroplast transit peptide. The plant and fungal coordinated responses provide a resourceful set of data and expand our understanding of the wheat-F. graminearum interaction.